It is proposed to study the HDL subclasses in man using the precipitation method developed in this laboratory for separation of HDL2 and HDL3. Attempts will be made to improve this method using precipitants other than dextran sulfate which is used in the current method. The subclasses of HDL will be characterized in terms of the isoforms of A-1 as determined by isoelectric focusing with quantitation of the several isoforms in patients with normal, low and elevated levels of HDL, and the distribution of isoforms in HDL2 and HDL3 will be compared. The distribution of the subclasses of HDL in patients with coronary heart disease, various types of diabetes and various types of hyperlipoproteinemia will be studied as will be the effects of treatment on the distribution of these subclasses. Studies in diabetic rats will be continued. In insulin deficient rats the nature of the defect of the removal mechanism will be investigated. In non-insulin deficient rats with islet cell transplants and in Zucker fatty rats where levels of serum insulin vary, the correlation with the levels of plasma triglycerides will be determined. In addition, further studies of the effect of cholesterol feeding in diabetic rats will be continued in order to determine the site of origin of the lipoproteins present in increased concentration in these animals and to learn the site of origin of these lipoproteins and to determine whether the persistence of elevated levels of these lipoproteins is due to increased formation or decreased removal of the lipoproteins.